Heat Shock Response

Abstract

In all organisms, a sudden increase in temperature leads to the accumulation of partially unfolded proteins which tend to
form life‐threatening aggregates within cells. These non‐native proteins induce the transiently increased expression of a
set of genes termed heat shock genes, and most of their products, designated as heat shock proteins, are involved in either
refolding or degradation of the non‐native proteins. This reaction is termed the heat shock response

The DnaK chaperone reaction cycle. The DnaK chaperone system consists of three proteins, DnaK, DnaJ and GrpE, and is involved
in the refolding of non‐native proteins. (a) The substrate‐binding domain of DnaJ binds a partially unfolded protein and transfers
it to the DnaK chaperone in its adenosine triphosphate (ATP)‐bound form (b). Next, the other domain of DnaJ binds to DnaK
to stimulate hydrolysis of ATP to adenosine diphosphate (ADP) and inorganic phosphate (Pi), thereby causing closing of the lid (c). Now, the protein starts to refold and, through interaction with GrpE, ADP is released
and replaced by ATP, the lid opens, and the protein is released (d). Either the protein is present in its active three‐dimensional structure
or, if not, it may enter another folding cycle.

Figure 2.

The GroE chaperone machine consists of two proteins, GroEL and GroES, and is involved in the refolding of non‐native proteins.
GroEL forms a double‐ring structure with two openings capable of accepting non‐native proteins, but not at the same time.
(a) A non‐native protein has entered the lower ring, each GroEL monomer has one molecule of adenosine triphosphate (ATP) bound
and the cavity has been closed by GroES. On the other side, the upper GroEL ring is open and able to accept another non‐native
protein molecule. (b) This molecule has entered the upper ring, which subseqently binds ATP and is sealed by GroES. At the
same time, the lower ring opens and releases its protein (c). Now, the lower ring is able to accept another non‐native protein
molecule, while the upper rings opens to release its protein into the environment. Under in vitro conditions, a complete folding cycle lasts about 15 s.

Figure 3.

Working model for the Clp complex. (a) ClpA and ClpX self‐assemble into oligomeric rings in the presence of adenosine triphosphate
(ATP), act as molecular chaperones, and accept specific non‐native substrate proteins to allow their refolding. (b) Either
one or two ClpA or ClpX rings can complex with two proteolytic ClpP rings. Non‐native proteins entering the ClpA or ClpX ring
are unfolded and transferred to the ClpP rings where their proteolysis into small peptides occurs.